基于转录组学的肝内胆管癌预后相关基因分析

目的 从转录组学层面研究肝内胆管癌(ICC)发生异常的生物学通路并发现与ICC预后相关的基因.方法 通过t检验和倍数变化法筛选差异表达基因并对相关基因进行KEGG功能富集分析;利用STRING数据库构建蛋白质互作网络,通过计算每个节点的度、介数和接近中心性来寻找网络的Hub节点;采用log-rank检验进行Kaplan...     

基于TCGA数据库和炎症相关基因构建前列腺癌预后模型

目的:探讨炎症相关基因对前列腺癌(PCa)患者预后的影响。方法:从癌症基因组图谱(TCGA)数据库下载PCa患者的临床资料和mRNA测序数据,分子特征数据库(MSigDB)下载炎症相关通路基因。通过单因素回归和LASSO回归分析筛选炎症基因构建预后风险模型,多因素回归分析筛选PCa独立预后因素构建列线图。根据列线图计算患者的风险评分,并以中位值分为高、低风险评分两组,识别差异表达基因进行富集分析。最后通过免疫组化染色验证PCa组织芯片中SPHK1的表达水平。结果:从172个候选基因筛选19个炎症相关基因构建预后风险模型,其中CD14、PIK3R5、GABBR1、RELA、IRF7、SCARF1、MSR1、SPHK1、OSM和STAB1是风险基因,AQP9、LPAR1、ATP2C1、NDP、CXCL6、P2RY2、DCBLD2、PCDH7和IFNAR1是保护基因。Kaplan-Meier分析显示高炎症评分组患者无复发生存期明显低于低炎症评分组患者,高风险评分患者的预后较低风险评分差。差异表达基因主要参与炎症通路的激活。免疫组化结果提示SPHK1在肿瘤组织中的表达高于正常组织,且随Glea...     

综合分析TCGA与GEO甲基化数据鉴定胆管癌预后相关基因SOX9和FZD10

目的 鉴定胆管癌(cholangiocarcinoma,CCA)甲基化与表达谱综合生物标志物,预测CCA患者预后.方法 从癌症基因组图谱(The Cancer Genome Atlas,TCGA)下载33例CCA样本和8例正常样本基因组甲基化数据及临床信息表达谱数据,同时从基因表达综合数据库(Gene Expressi...     

肝切除切缘的距离对肝内胆管癌伴乙型肝炎肝硬化预后的影响

目的分析肝切除手术切缘的距离对肝内胆管癌伴乙型肝炎肝硬化患者的近期和远期预后的影响。方法回顾性分析东方肝胆外科医院306例ICC伴乙型肝炎肝硬化肝切除患者的临床病理资料。应用Kaplan-Meier法描绘无复发生存(recurrent free survival,RFS)和整体生存(overall survival,OS)曲线,Cox回归模型分析影响其预后的因素。结果 R1组患者39例(12.7%),阴性切缘组(R0)中,≥10 mm为宽切缘组87例和1~9 mm为窄切缘组180例。随访期间,209例(68.3%)患者出现复发。总体的中位和5年的RFS和OS分别为13.8月,24%和21.3月,28%。R1切除提示较差的RFS(P=0.002)和OS(P=0.006)。窄切缘相对于宽切缘提示更低的RFS(P=0.025),而OS(P=0.254)无差别。结论 R1切除是肝内胆管癌伴乙型肝炎肝硬化的患者长期预后的独立危险因素。推荐肝切除时尽可能保证大于10 mm的手术切缘改善预后。     

肝内胆管癌18例临床分析

目的: 提高肝内胆管癌的诊治水平.方法: 回顾分析1990年以来18例肝内胆管癌临床资料.结果: 肝内胆管癌缺乏特异性的症状;1990年1月~2000年3月的11例肝内胆管癌全部误诊,2000年4月~2004年3月的7例经CT检查和B超引导肝穿刺活检明确诊断,其中2例为迟发性肝内胆管癌;左肝内胆管癌12例,右肝内胆管癌6例;随访15例,3个月、6个月及1年生存率分别为80.0%(12/15),66.7%(10/15)和53.3%(8/15);9例肝叶切除术和6例非肝叶切除术患者的1年生存率分别为77.8%(7/9)和16.7%(1/6)(P=0.039).结论: CT检查结合B超引导肝穿刺活检能帮助明确诊断肝内胆管癌,肝叶切除可改善预后.     

肝内胆管癌病人肝脏手术切缘与预后的关系

目的：分析肝脏手术切缘对肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)病人预后的影响,并探索ICC切缘推荐距离。方法：收集2011年1月至2017年1月北京肿瘤医院肝胆外科ICC病人的临床病理资料。用单因素和多因素Cox分析影响ICC预后的危险因素,并用Kaplan-Meier方法制作无复发生存(recurrent free survival,RFS)期和总生存(overall survival,OS)期曲线。采用限制性立方样条(restricted cubic spline,RCS)分别探索R0切缘距离与OS期和RFS期的关系,并探索手术切缘推荐距离。结果：本研究共71例病人,随访2～107个月,中位RFS期8个月,中位OS期17个月。1、3、5年的RFS率分别为35%、20%、10%,OS率分别为68%、38%、23%。Cox回归分析发现,美国癌症联合委员会(American Joint Committee on Cancer,AJCC)分期、手术切缘、甲胎蛋白(alpha-fetoprotein,AFP)、糖类抗原19-9(carbohydr...     

淋巴结清扫对肝内胆管癌预后价值的Meta分析

目的 评价淋巴结清扫（LND）对肝内胆管癌患者预后的影响。方法 检索2012年1月至2022年10月间PubMed、EmBase、Web of Science、Cochrane、万方数据、中国知网数据库收录的文献,将肝内胆管癌手术治疗患者分为淋巴结清扫组（LND+组）及未行淋巴结清扫组（LND-组）。分析LND对患者预后的影响。结果 共纳入21篇文献5 449例患者。LND并未改善患者总生存期（OS）,清扫淋巴结阳性组（N1组）患者OS低于LND-组（HR=2.75,95%CI:1.73～4.36,P<0.05）,清扫淋巴结阴性组（N0组）患者OS高于N1组患者（HR=0.35,95%CI:0.31～0.40,P<0.001）,与LND-组患者OS差异无统计学意义。亚组分析结果提示,LND能显著提高R0切除亚组中患者的OS(HR=0.60,95%CI:0.44～0.81,P<0.01),但并不能改善临床淋巴结阴性亚组和非R0切除亚组患者的OS;R0切除亚组中,N0组患者OS高于LND-组（HR=0.75,95%CI:0.58～0.97,P<0.05）。LND+组...     

术前外周血肝纤维化血清学指标对肝内胆管癌预后预测价值研究

目的 探讨术前外周血反映肝纤维化血清学指标对肝内胆管癌根治性切除术后病人预后预测价值.方法 回顾性分析2010年1月至2018年12月于西安交通大学第一附属医院肝胆外科因肝内胆管癌行根治性切除术的124例病人的临床病理资料.采用ROC曲线确定天冬氨酸氨基转移酶血小板比值指数(APRI)、γ-谷氨酰转肽酶血小板比值指数(...     

肝内胆管癌临床研究现状

肝内胆管癌（ICC）的病因复杂，且高度侵袭、高度异质、预后不良。近年来ICC的临床诊断与治疗进展显著，主要包括功能与分子影像学技术提供了更精准的术前评估与复发监测新手段；分子分型与传统临床病理学分型结合为ICC的临床决策提供了更精准保障。手术切除仍是ICC的惟一根治性治疗手段，对R0切除、淋巴结清扫、术后辅助治疗以及复发再切除的意义得到肯定。局部治疗、分子靶向治疗及免疫治疗等新型疗法发展迅速，为晚期ICC带来新的希望。传统治疗手段与新型疗法的序贯、联合，“多兵种联合作战”是未来发展方向。     

基于TCGA数据库胆管癌自噬-临床预后模型的构建和评估

目的 探讨自噬相关基因（autophagy-related genes,ATGs）在临床预后方面的价值,并构建自噬基因的预后风险模型,评估胆管癌（cholangiocarcinoma,CCA）患者的生存及预后状况。方法 在癌症基因组图谱数据库（TCGA）中下载CCA的转录组数据和临床数据,从人类自噬数据库（HADb）中提取自噬相关基因,筛选出CCA样本中差异表达的自噬相关基因（DEATGs）;GO富集分析与KEGG通路分析进一步阐明DEATGs在CCA中的作用;通过Cox回归分析构建自噬预后风险评分模型,并运用生存分析、风险曲线、ROC曲线及独立预后分析验证预后模型的准确性。结果 CCA组织样本和非肿瘤组织样本一共筛选出49 个DEATGs（上调的基因48 个,下调的基因1 个）;通过单因素Cox回归分析及多因素Cox回归分析筛选出5个最有预后价值的基因（RHEB、PPP1R15A、ATG101、BNIP3、NRG1）,并基于这5个基因构建自噬预后风险评分模型,模型公式为：风险值=NRG1表达量×1.1207+BNIP3表达量×1.4002+ATG101表达量×1.3457-PPP1R15A表达量×1.1613-RHEB表达量×1.3279。生存分析表明低风险组的生存率要显著高于高风险组,风险曲线表明患者风险值与生存时间及生存状态显著相关,ROC曲线提示自噬预后模型具有良好的准确性,是一个独立的预后因素（HR 1.427,95%CI 1.161～1.756,P＜0.001）。结论 5个自噬基因（RHEB、PPP1R15A、ATG101、BNIP3、NRG1）构建的自噬相关预后风险模型,可以有效预测CCA患者的预后情况。     

Surgical management of intrahepatic cholangiocarcinoma: A 31-year experience

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver. It is, though, a rare tumor and little is known regarding its natural history, clinicopathologic characteristics, or the outcomes of surgical therapy. We reviewed the experience of 61 patients with ICC seen by the surgical service at the Mayo Clinic over a 31-year period. Patient demographic and clinical data were recorded, as were survival statistics. Pathologic data were also obtained and patients stratified according to the TNM classification. Twenty-eight patients were resected for cure. Overall, 45 patients died of ICC. Of the patients resected for cure, survival at 3 years was 60%. No pathologic condition was found to be associated with the development of ICC. Overall survival correlated with stage of the tumor. Among patients resected for cure, stage did not correlate with survival. Prognosis for patients with ICC remains poor; resection, though, appears to prolong survival. Received for publication on May 8, 1997; accepted on July 3, 1997     

周围型肝内胆管细胞癌的诊断和治疗

目的 探讨周围型肝内胆管细胞癌(PICC)的诊断及外科治疗，提高其诊治水平。方法 总结分析1991～2000年间我科收治的46例PICC病人诊断、治疗及预后的资料。结果 (1)本病早期无特异性临床表现，部分病例可并存乙型肝炎(20％)、肝硬化(45％)，部分伴有肝内胆管结石(20％)，血清AFP升高(30％)；(2)影像学检查：B超、CT、MRI的诊断率分别为90．0％、95．4％及100．0％；(3)手术切除率为64．0％．全组病例的1、3、5年生存率分别为60．0％、33．0％及26．0％；(4)生存5年以上的12例病人中，直径≤3cm的小肝癌9例，包膜完整的肿块型直径位于3～5cm肝癌3例，术后均辅助性放射治疗和选择性肝动脉灌注化疗。结论影像学检查能在早、中期提供临床线索，但缺乏特异性血清肿瘤标志物，治愈性切除术加辅助治疗可获得良好生存率。     

肝内胆管细胞癌诊治策略

肝内胆管细胞癌（intrahepatic cholangiocarcinoma, ICC）的生物学特性与肝细胞癌和肝外胆管癌存在显著差异,早期缺乏明显临床表现。因此,对合并高危因素的人群进行定期筛查,有助于ICC的早期诊断和及时治疗。现有ICC分期系统为预后评估提供了临床依据,但是在影响病人预后因素方面尚存在分歧,有待大规模前瞻性研究提供循证医学证据,进一步修订、完善分期系统。以手术为主的综合治疗是ICC的主流治疗模式,根治性切除和淋巴结清扫有助于提高疗效、改善病人预后,非手术治疗方法的不断进展可使无法手术或术后复发ICC病人临床获益。     

末梢型肝内胆管细胞癌的诊断及外科治疗效果分析

目的 探讨末梢型肝内总胆管细胞癌（PIHCC）的诊断及外科治疗结果,以提高其诊治水平。方法 回顾性分析1970－1999年间外科治疗的20例PIHCC患者诊断、治疗及预后的资料。结果 （1）本病缺乏特异性临床表现,部分病例可并发乙型肝炎（35．0％）、肝硬化（45．0％）和血清AFP升高（25．0％）;（2）影像学检查：B超、CT、MRI及ECT的诊断率分别为90．0％（18／20）、94．4％（17／18）、3／3及4／3;（3）手术切除率为60％,全组病例的1、3、5年生存率分别为55．0％（11／20）、35．0％（7／20）及20．0％（4／20）,其中肝切除术病例分别为83．3％（11／12）、58．3％（7／12）、33．3％（4／12）;（4）生存5年以上的4例患者中,直径≤3cm的小肝癌3例、包膜完整的结节型大肝癌1例,且术后均辅助选择性肝动脉灌注化疗,有助于生存率的提高。结论 本病缺乏特异性血清肿瘤标志物,治愈性切除术（包括术后辅助治疗）可获得良好生存率。     

末梢型肝内胆管细胞癌的诊治分析

目的探讨末梢型肝内胆管细胞癌的诊断和治疗方法，评价淋巴清扫在末梢型肝内胆管细胞癌手术中的意义。方法回顾性分析我院1993年1月至2003年4月手术治疗28例末梢型肝内胆管细胞癌的临床资料，对发病特点，症状体征，影像学检查，病理特点和手术治疗效果进行分析。结果单因素生存分析显示手术切除组1，3，5年生存率分别为78．9％，36．8％，21．1％，未切除组15．8％，0，0，两组有显著性差异（P〈0．001）。进行淋巴结清扫组1，3，5年生存率分别为100％，60％，40％，未进行淋巴结清扫切除组为55．5％，11．1％，0，两组有显著性差异（P〈0．001）。合并门静脉癌栓组1，3，5年生存率分别为50％，0，0，未合并门静脉癌栓组为86．7％，46．7％，26．7％，两组有显著性差异（P=0．004）。而COX比例风险回归模型多因素分析显示手术切除和淋巴清扫与预后显著相关，而门静脉癌栓与生存没有显著相关性。结论淋巴转移，手术切除是影响生存的主要因素，手术切除能改善预后，术中进行肝门淋巴脂肪清扫能提高术后生存率。     

术中联合淋巴结清扫对肝内胆管细胞癌预后影响的荟萃分析

目的评价术中联合淋巴结清扫术能否提高肝内胆管细胞癌预后。方法计算机检索2005年1月1日至2015年3月31日期间PubMed、EmBase、Web of Science、中国知网、维普、万方数据库收录的比较肝内胆管细胞癌根治术中是否联合淋巴结清扫术对预后影响的文献,文献纳入由两名研究者独立筛选,经过质量评价与数据提取后,采用RevMan5.3进行Meta分析。结果共纳入5篇队列研究,纳入病例总数522例,其中行淋巴结清扫术[LND(+)]272例,未行淋巴结清扫术[LND(-)]250例。Meta分析显示术后3年总生存(RR=0.91,95%CI:0.74~1.13,P=0.41),术后5年总生存率(RR=0.84,95%CI:0.63~1.11,P=0.22),术后3年无瘤生存率(RR=0.89,95%CI:0.65~1.21,P=0.47)。结论术中常规联合淋巴结清扫术对肝内胆管细胞癌预后无明显影响。     

Clinical experience of intrahepatic cholangiocarcinoma associated with hepatolithiasis

Between 1960 and 1986, seven patients with intrahepatic cholangiocarcinoma and one patient with intrahepatic bile duct adenoma, related to hepatolithiasis, were seen among 112 cases of hepatolithiasis. Histopathologically, the tumors associated with hepatolithiasis arose from the periphery of the stone-containing bile duct, spread chiefly along the luminal surface, and invaded the ductal wall or periductal tissue. The tumors showed papillary to papillo-tubular proliferation and were diagnosed as the intraductal or periductal spreading type of cholangiocarcinoma. In addition, atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that chronic relapsing cholangitis in patients with hepatolithiasis can induce progressive changes to atypical epithelial hyperplasia which may develop into cholangiocarcinoma.     

Serosal invasion in TNM staging of mass-forming intrahepatic cholangiocarcinoma

Background/Purpose The Liver Cancer Study Group of Japan established a tumor-nodule-metastasis (TNM) staging system for mass-forming intrahepatic cholangiocarcinoma, with T determined by tumor number and size and vascular or serosal invasion. Serosal invasion is not considered in the designation established by the International Union Against Cancer. Methods Sixty-three patients who underwent hepatic resection for mass-forming intrahepatic cholangiocarcinoma were investigated retrospectively, with the investigation including univariate and multivariate analyses of potential prognostic factors. Results By log-rank test, tumor size more than 3.0 cm, vascular invasion, lymph node metastasis, intrahepatic metastasis, and involved resection margin, but not serosal invasion, were associated significantly with poor prognosis. Even in patients with serosal invasion, the postoperative outcome was much better in those without than in those with vascular invasion. Multivariate analysis identified vascular invasion, lymph node metastasis, and an involved resection margin as independent prognostic factors. When serosal invasion was excluded from tumor staging, the 5-year survival rates became more clearly stratified: 100% in those with stage I disease, 62% in those with stage II, 25% in those with stage III, and 7% for patients with stage IV. Conclusions Serosal invasion showed no survival impact after hepatic resection for mass-forming intrahepatic cholangiocarcinoma. When serosal invasion was omitted from the TNM staging proposed by the Liver Cancer Study Group of Japan, stratification of postoperative survival between stages was more effective.     

Macroscopic classification and preoperative diagnosis of intrahepatic cholangiocarcinoma in Japan

We reviewed the records of 64 patients with resected intrahepatic cholangiocarcinoma (ICC) according to the macroscopic classification proposed by the Liver Cancer Study Group of Japan, in which ICC is classified into three types based on the macroscopic appearance of the cut sur-face of the tumor: mass-forming, periductal-infiltrating, and intraductal growth types. There were 24 patients with the periductal-infiltrating type, 28 with the mass-forming type, and 12 with the intraductal growth type. The mass-forming type essentially showed expansive growth irrespective of hilar invasion. The periductal-infiltrating type of tumor exhibited diffuse infiltration along the portal pedicle, and preoperative planning of the resection procedure was similar to that for primary bile duct carcinoma of the hepatic confluence. Vascular resection and reconstruction was required in some patients with advanced disease. In the intraductal growth type of tumor, precise determination of tumor extent was difficult because of the ambiguity caused by abundant mucin secreted by the tumor and/or by the superficial mucosal spread of the tumor along the bile duct. Percutaneous transhepatic cholangioscopy provided the most reliable information for designing the operative procedure. The macroscopic classification is useful for preoperative diagnosis of tumor extent and for planning the surgical procedure. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998